To identify genetic loci determining alcoholism, we have focused on human and murine behaviors associated with serotonin function. We have studied candidate genetic loci involved in serotonin function including tryptophan hydroxylase, serotonin receptors and the serotonin transporter. After cloning tryptophan hydroxylase from mouse mastocytoma cells, we showed that this cDNA recognized brainstem mRNA for this rate-limiting enzyme of serotonin synthesis. The TrpOHas gene was located to mouse chromosome 7. Cloning and sequencing of the 21 kilobase gene allowed the delineation of its putative regulatory sequences as well as its intron/exon boundaries. Genetic studies of the serotonin receptors have been performed in deer mice. The serotonin transporter was functionally expressed in Xenopus oocytes, allowing us to approach the molecular cloning of this gene.